Anterior cingulate folding pattern is altered in autism spectrum disorder

Abstract

Neuroimaging research has identified focal differences in the cerebral cortex of individuals with autism spectrum disorder (ASD), particularly in the cortical folds (sulci) within higher-level association cortices. The present study investigated the sulcal patterning and morphology of the anterior cingulate cortex (ACC) in individuals with ASD compared to neurotypical (NT) individuals for the first time. We used neuroimaging data from 50 NT and 50 ASD participants. All participants were under 20 years old and male. The two groups were age-matched. Using established criteria and cortical reconstructions generated from each participant's T1-weighted magnetic resonance imaging scans with FreeSurfer, we identified the defining sulcal feature of ACC, the variably present paracingulate sulcus (PCGS): its presence in the left and right hemispheres, and asymmetry in PCGS presence between hemispheres. Finally, multiple quantitative morphological features (length, depth, and cortical thickness mean and standard deviation) were extracted from the PCGS using FreeSurfer tools. Analyses revealed that NT participants were more likely to have asymmetrical PCGS patterns than ASD participants (controlling for age and scanner site). However, none of the quantitative morphological features differed between groups. These findings suggest the presence of a variation in the prenatal neurodevelopment of ACC in young males with ASD; however, further research is necessary to uncover the role of this observed difference in the pathogenesis of ASD. The present study also adds to the growing literature implicating variations in PCGS patterning as a trait marker across multiple disorders.

Keywords: Anterior cingulate cortex; Autism spectrum disorder; Cortical folding; Magnetic resonance imaging; Neuroanatomy; Neurodevelopment; Sulci.

Figure 1.. Examples of ACC Sulcal Patterning.

ACC sulcal patterning is defined by the presence/absence of the PCGS, which runs dorsal and parallel to the CGS when present (CGS: blue; PCGS: orange). The images depict the intra-hemispheric presence/absence (rows) and inter-hemispheric asymmetry/symmetry (columns) of the PCGS in four example NT participants (columns) on the pial (i.e., wrinkled) FreeSurfer cortical surface reconstructions (Dale et al., 1999; Fischl et al., 1999). Sulci are dark gray and gyri are light gray. Abbreviations are as follows: anterior cingulate cortex (ACC), cingulate sulcus (CGS), paracingulate sulcus (PCGS).

Figure 2.. Differences in PCGS hemispheric incidence and asymmetry between NT and ASD individuals.

(A) Bar plot visualizing PCGS incidence as a function of hemisphere (x-axis), group, and presence (colors; see key). (B) Bar plot visualizing PCGS incidence as a function of group (x-axis) and asymmetry (colors; see key). Upper asterisk denotes GLM results for between-group comparisons of asymmetry, while lower asterisks depict McNemar test results for within-group comparisons of asymmetry. In both (A) and (B), the percentages are included above each column (n = 50 in each group). Abbreviations are as follows: autism spectrum disorder (ASD), group, neurotypical (NT), paracingulate sulcus (PCGS). Asterisks indicate the following p-value thresholds: *** p < 0.001, * p < 0.05, n.s. p > .05.